1991 Fiscal Year Final Research Report Summary
Study on functinal domains of von Willebrand (vW) factor in patients with vW disease.
Grant-in-Aid for General Scientific Research (C)
|Allocation Type||Single-year Grants |
|Research Institution||Nara Medical University (1991)|
The University of Tokyo (1989-1990)
TAKAHASHI Yukihiro Nara Medical University, Pediatrics, Associate Professor -> 奈良県立医科大学, 医学部, 助教授 (60142379)
|Project Period (FY)
1989 – 1991
|Keywords||von Willebrand factor / von Willebrand disease|
I. The analysis of functional domains of von Willebrand factor(vWf) and the production and characterization of monoclonal antibodies (MAbs) against vWf.
A. the factorVIII-binding domain: vWf-plasmin or trypsin digested fragment p-34(amino acid residue 1-298(273)) was purified using DEAE and Heparin column. 4 different MAbs against p-34 were produced by D.Meyer, INSERM 143 France, collaborated with me. Now, I'm going to characterize these antibodies
B. Platelet glycoprotein Ib(GPIb)-binding domain: Two different MAbs (NMC/vW4 from our lab. 322 from france) against vWf which inhibit the binding of vWf to GPIb were characterized, and I discovered the different functional site of GPIb-binding of vWf by two inducers, such as antibiotics ristocetin and venom factor botrocetin. and Aurin tricarboxylic acid (ATA) is known to inhibit ristocetin-induced platelet aggregation but not the other platelet aggregaters. Its capacity to abolish human vWf-platelet interaction was further in vestigated and was found that ATA which blocks the vWf/GPIb pathway by interfering with vWf and not with platelet, is a potential tool in prevention the early stages of thrombosis
C. Human collagen-binding domain: One MAb(NMC/vW3) which inhibit the vWf-human typeIII fibrilar collagen binding was discovered and was shown the epitope in vWf subunit. That is, The epitope was localized between the amino acid residue 911 and 1365.
II. The analysis of plasma von Willebrand factor in von Willebrand disease. I studied on the establishment of several vWf function assays and vWf protein analysis of plasma vWf in normal and several types of von Willebrand disease.
A. The vWf-human collagen binding assay, using a minute plasma was established. The abnormality of the collagen- binding in type II vWd was discovered.
B. The analytical method of vWf subunit in plasma vWf using a minute sample was established. Now the plasma vWf in several types of vWd is going to examine.
Research Products (6 results)